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Case report: Crigler-Najjar syndrome type 1 in Croatia—more than a one in a million: a case series

Crigler-Najjar syndrome (CNS) is an exceedingly rare autosomal recessive disease with an estimated incidence of 1 in a million live births. CNS type 1 (CNS1) is the most severe form, characterized by severe unconjugated hyperbilirubinemia since birth due to the absence of hepatic uridine 5'-dip...

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Autores principales: Kovačić Perica, Matea, Todorić, Ivana, Marčinković, Nedo, Džepina, Petra, Aničić, Mirna Natalija, Mrzljak, Anna, Vuković, Jurica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620791/
https://www.ncbi.nlm.nih.gov/pubmed/37928349
http://dx.doi.org/10.3389/fped.2023.1276349
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author Kovačić Perica, Matea
Todorić, Ivana
Marčinković, Nedo
Džepina, Petra
Aničić, Mirna Natalija
Mrzljak, Anna
Vuković, Jurica
author_facet Kovačić Perica, Matea
Todorić, Ivana
Marčinković, Nedo
Džepina, Petra
Aničić, Mirna Natalija
Mrzljak, Anna
Vuković, Jurica
author_sort Kovačić Perica, Matea
collection PubMed
description Crigler-Najjar syndrome (CNS) is an exceedingly rare autosomal recessive disease with an estimated incidence of 1 in a million live births. CNS type 1 (CNS1) is the most severe form, characterized by severe unconjugated hyperbilirubinemia since birth due to the absence of hepatic uridine 5'-diphosphate glucuronyltransferase (UGT1A1) activity. Daily phototherapy (PT) and liver transplant (LT) are the mainstays of therapy. Here, we present a higher-than-expected incidence of CNS1 in Croatia (6,1 in a million). In the last 31 years, we treated eight CNS1 patients from five families with no reported consanguinity. Four patients are descendants of an isolated enclave in Kosovo with a small gene pool and a high potential for inbreeding. Severe unconjugated hyperbilirubinemia was verified in a neonatal period and PT was initiated. Four patients underwent LT from living-related donors. One of them had unsuccessful hepatocyte transplantation earlier. LT was successful in three patients, and one patient died due to primary graft dysfunction. Four patients are currently treated with 9–12 h daily PT with inconsistent disease control, and gradually increasing bilirubin. One patient developed kernicterus before LT, while others have normal psychomotor development and no neurologic impairment. Genetic testing of the UGT1A1 gene in six patients from three families revealed three different homozygous mutations (c.722_723 delAG, c.717_718 delAG, and c.1021 C >T), all previously described in other populations. There is a possibility of the founder effect as an explanation for the higher incidence of CNS1 in at least a subgroup of Croatians.
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spelling pubmed-106207912023-11-03 Case report: Crigler-Najjar syndrome type 1 in Croatia—more than a one in a million: a case series Kovačić Perica, Matea Todorić, Ivana Marčinković, Nedo Džepina, Petra Aničić, Mirna Natalija Mrzljak, Anna Vuković, Jurica Front Pediatr Pediatrics Crigler-Najjar syndrome (CNS) is an exceedingly rare autosomal recessive disease with an estimated incidence of 1 in a million live births. CNS type 1 (CNS1) is the most severe form, characterized by severe unconjugated hyperbilirubinemia since birth due to the absence of hepatic uridine 5'-diphosphate glucuronyltransferase (UGT1A1) activity. Daily phototherapy (PT) and liver transplant (LT) are the mainstays of therapy. Here, we present a higher-than-expected incidence of CNS1 in Croatia (6,1 in a million). In the last 31 years, we treated eight CNS1 patients from five families with no reported consanguinity. Four patients are descendants of an isolated enclave in Kosovo with a small gene pool and a high potential for inbreeding. Severe unconjugated hyperbilirubinemia was verified in a neonatal period and PT was initiated. Four patients underwent LT from living-related donors. One of them had unsuccessful hepatocyte transplantation earlier. LT was successful in three patients, and one patient died due to primary graft dysfunction. Four patients are currently treated with 9–12 h daily PT with inconsistent disease control, and gradually increasing bilirubin. One patient developed kernicterus before LT, while others have normal psychomotor development and no neurologic impairment. Genetic testing of the UGT1A1 gene in six patients from three families revealed three different homozygous mutations (c.722_723 delAG, c.717_718 delAG, and c.1021 C >T), all previously described in other populations. There is a possibility of the founder effect as an explanation for the higher incidence of CNS1 in at least a subgroup of Croatians. Frontiers Media S.A. 2023-10-19 /pmc/articles/PMC10620791/ /pubmed/37928349 http://dx.doi.org/10.3389/fped.2023.1276349 Text en © 2023 Kovačić Perica, Todorić, Marčinković, Džepina, Aničić, Mrzljak and Vuković. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Kovačić Perica, Matea
Todorić, Ivana
Marčinković, Nedo
Džepina, Petra
Aničić, Mirna Natalija
Mrzljak, Anna
Vuković, Jurica
Case report: Crigler-Najjar syndrome type 1 in Croatia—more than a one in a million: a case series
title Case report: Crigler-Najjar syndrome type 1 in Croatia—more than a one in a million: a case series
title_full Case report: Crigler-Najjar syndrome type 1 in Croatia—more than a one in a million: a case series
title_fullStr Case report: Crigler-Najjar syndrome type 1 in Croatia—more than a one in a million: a case series
title_full_unstemmed Case report: Crigler-Najjar syndrome type 1 in Croatia—more than a one in a million: a case series
title_short Case report: Crigler-Najjar syndrome type 1 in Croatia—more than a one in a million: a case series
title_sort case report: crigler-najjar syndrome type 1 in croatia—more than a one in a million: a case series
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620791/
https://www.ncbi.nlm.nih.gov/pubmed/37928349
http://dx.doi.org/10.3389/fped.2023.1276349
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